ESTRR
MCID: EST007
MIFTS: 37

Estrogen Resistance (ESTRR)

Categories: Bone diseases, Endocrine diseases, Genetic diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Estrogen Resistance

MalaCards integrated aliases for Estrogen Resistance:

Name: Estrogen Resistance 58 76 30 13 6 41 74
Estrogen Resistance Syndrome 60 38 17
Estrogen Insensitivity 58 76
Estrr 58 76

Characteristics:

Orphanet epidemiological data:

60
estrogen resistance syndrome
Inheritance: Autosomal recessive;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
based on 2 reported patients, 1 male and 1 female (last curated august 2013)


HPO:

33
estrogen resistance:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Estrogen Resistance

UniProtKB/Swiss-Prot : 76 Estrogen resistance: A disorder characterized by partial or complete resistance to estrogens, in the presence of elevated estrogen serum levels. Clinical features include absence of the pubertal growth spurt, delayed bone maturation, unfused epiphyses, reduced bone mineral density, osteoporosis, continued growth into adulthood and very tall adult stature. Glucose intolerance, hyperinsulinemia and lipid abnormalities may also be present.

MalaCards based summary : Estrogen Resistance, also known as estrogen resistance syndrome, is related to aromatase deficiency and breast cancer. An important gene associated with Estrogen Resistance is ESR1 (Estrogen Receptor 1), and among its related pathways/superpathways are Endocrine resistance and Prolactin signaling pathway. Affiliated tissues include bone, breast and ovary, and related phenotypes are osteopenia and osteoporosis

OMIM : 58 Estrogen resistance (ESTRR) is characterized by absence of puberty with elevated estradiol and gonadotropic hormones, as well as markedly delayed bone maturation. Female patients show absent breast development, small uterus, and enlarged multicystic ovaries; male patients may show small testes (Bernard et al., 2017). Some patients exhibit continued growth into adulthood (Smith et al., 1994). (615363)

Wikipedia : 77 Estrogen insensitivity syndrome (EIS), or estrogen resistance, is a form of congenital estrogen... more...

Related Diseases for Estrogen Resistance

Diseases related to Estrogen Resistance via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 aromatase deficiency 11.5
2 breast cancer 10.3
3 wilms tumor 5 9.8
4 wilms tumor 6 9.8
5 estrogen-receptor positive breast cancer 9.8
6 colorectal cancer 9.6
7 leukemia 9.6
8 lymphoma 9.6
9 endometriosis of ovary 9.5 ESR1 TRERF1

Graphical network of the top 20 diseases related to Estrogen Resistance:



Diseases related to Estrogen Resistance

Symptoms & Phenotypes for Estrogen Resistance

Human phenotypes related to Estrogen Resistance:

60 33 (show all 26)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 osteopenia 60 33 hallmark (90%) Very frequent (99-80%) HP:0000938
2 osteoporosis 60 33 hallmark (90%) Very frequent (99-80%) HP:0000939
3 increased circulating gonadotropin level 60 33 hallmark (90%) Very frequent (99-80%) HP:0000837
4 primary amenorrhea 60 33 hallmark (90%) Very frequent (99-80%) HP:0000786
5 absence of secondary sex characteristics 60 33 hallmark (90%) Very frequent (99-80%) HP:0008187
6 enlarged polycystic ovaries 60 33 hallmark (90%) Very frequent (99-80%) HP:0008675
7 overgrowth 60 33 hallmark (90%) Very frequent (99-80%) HP:0001548
8 hypoplasia of the uterus 60 33 hallmark (90%) Very frequent (99-80%) HP:0000013
9 breast hypoplasia 60 33 hallmark (90%) Very frequent (99-80%) HP:0003187
10 marked delay in bone age 60 33 hallmark (90%) Very frequent (99-80%) HP:0003799
11 delayed epiphyseal ossification 60 33 hallmark (90%) Very frequent (99-80%) HP:0002663
12 absence of pubertal development 60 33 hallmark (90%) Very frequent (99-80%) HP:0008197
13 acanthosis nigricans 60 33 frequent (33%) Frequent (79-30%) HP:0000956
14 acne 60 33 frequent (33%) Frequent (79-30%) HP:0001061
15 glucose intolerance 60 33 frequent (33%) Frequent (79-30%) HP:0001952
16 hyperinsulinemia 60 33 frequent (33%) Frequent (79-30%) HP:0000842
17 episodic abdominal pain 60 33 frequent (33%) Frequent (79-30%) HP:0002574
18 elevated tissue non-specific alkaline phosphatase 60 33 frequent (33%) Frequent (79-30%) HP:0010679
19 coronary artery atherosclerosis 33 frequent (33%) HP:0001677
20 delayed skeletal maturation 33 HP:0002750
21 tall stature 60 Very frequent (99-80%)
22 abnormality of the adrenal glands 60 Excluded (0%)
23 coronary atherosclerosis 60 Frequent (79-30%)
24 abnormality of circulating hormone level 60 Very frequent (99-80%)
25 abnormal testosterone level 60 Excluded (0%)
26 abnormality of the pubic hair 60 Excluded (0%)

Symptoms via clinical synopsis from OMIM:

58
Skeletal:
osteopenia
delayed bone age (in male and female patients)
low trabecular volumetric bone density (in male patient)
low cortical volumetric bone density (in male patient)

Growth Height:
continued growth into adulthood (in male and female patients)

Chest Breasts:
absent breast development
breast development unresponsive to oral estrogen

Skeletal Spine:
decreased bone mineral density of lumbar spine (in male patient)

Skin Nails Hair Skin:
acanthosis nigricans, axillary (in male patient)
severe facial acne (in female patient)

Genitourinary Internal Genitalia Female:
primary amenorrhea
small uterus
large multicystic ovaries

Cardiovascular Heart:
early atherosclerosis of coronary artery (in male patient)

Genitourinary External Genitalia Female:
tanner stage 4 pubic hair

Skeletal Limbs:
incomplete epiphyseal closures in adulthood (in male and female patients)

Endocrine Features:
elevated serum estradiol (in male and female patients)
elevated serum estrone (in male and female patients)
elevated serum follicle-stimulating hormone (in male and female patients)
elevated serum luteinizing hormone (in male and female patients)
hyperinsulinemia (in male patient)
more

Clinical features from OMIM:

615363

GenomeRNAi Phenotypes related to Estrogen Resistance according to GeneCards Suite gene sharing:

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-2 9.02 BCAR1 BCAR3
2 Decreased viability GR00381-A-1 9.02 BCAR3
3 Decreased viability GR00402-S-2 9.02 BCAR1 BCAR3

Drugs & Therapeutics for Estrogen Resistance

Search Clinical Trials , NIH Clinical Center for Estrogen Resistance

Genetic Tests for Estrogen Resistance

Genetic tests related to Estrogen Resistance:

# Genetic test Affiliating Genes
1 Estrogen Resistance 30 ESR1

Anatomical Context for Estrogen Resistance

MalaCards organs/tissues related to Estrogen Resistance:

42
Bone, Breast, Ovary, Uterus, Testes, Adrenal Gland, B Cells

Publications for Estrogen Resistance

Articles related to Estrogen Resistance:

(show all 27)
# Title Authors Year
1
TGF-I^ Stimulation of EMT Programs Elicits Non-genomic ER-I+ Activity and Anti-estrogen Resistance in Breast Cancer Cells. ( 28955730 )
2017
2
Human enhancer of filamentation 1-induced colorectal cancer cell migration: Role of serine phosphorylation and interaction with the breast cancer anti-estrogen resistance 3 protein. ( 25817040 )
2015
3
A new class of small molecule estrogen receptor-alpha antagonists that overcome anti-estrogen resistance. ( 26575173 )
2015
4
Breast Cancer Anti-Estrogen Resistance 4 (BCAR4) Drives Proliferation of IPH-926 lobular Carcinoma Cells. ( 26317614 )
2015
5
Stromal cells promote anti-estrogen resistance of breast cancer cells through an insulin-like growth factor binding protein 5 (IGFBP5)/B-cell leukemia/lymphoma 3 (Bcl-3) axis. ( 26515727 )
2015
6
Anti-estrogen Resistance in Human Breast Tumors Is Driven by JAG1-NOTCH4-Dependent Cancer Stem Cell Activity. ( 26387946 )
2015
7
Breast cancer anti-estrogen resistance 3 inhibits transforming growth factor I^/Smad signaling and associates with favorable breast cancer disease outcomes. ( 25499443 )
2014
8
Expression of breast cancer anti-estrogen resistance 1 in relation to vascular endothelial growth factor, p53, and prognosis in esophageal squamous cell cancer. ( 22816673 )
2013
9
Delayed puberty and estrogen resistance in a woman with estrogen receptor alpha variant. ( 23841731 )
2013
10
Reproductive endocrinology: ESR1 mutation causes estrogen resistance and puberty delay in women. ( 23897169 )
2013
11
Breast-cancer anti-estrogen resistance 4 (BCAR4) encodes a novel maternal-effect protein in bovine and is expressed in the oocyte of humans and other non-rodent mammals. ( 23202989 )
2013
12
Paradoxical roles for FOXA1 in anti-estrogen resistance and as a luminal differentiation factor in breast cancer. ( 25083421 )
2012
13
Breast cancer anti-estrogen resistance 3 (BCAR3) protein augments binding of the c-Src SH3 domain to Crk-associated substrate (p130cas). ( 22711540 )
2012
14
Breast cancer anti-estrogen resistance protein 1 (BCAR1/p130cas) in pulmonary disease tissue and serum. ( 21469768 )
2011
15
Anti-estrogen resistance in breast cancer is induced by the tumor microenvironment and can be overcome by inhibiting mitochondrial function in epithelial cancer cells. ( 22041887 )
2011
16
Trefoil factor 3 is oncogenic and mediates anti-estrogen resistance in human mammary carcinoma. ( 21170268 )
2010
17
Selective recruitment of breast cancer anti-estrogen resistance genes and relevance for breast cancer progression and tamoxifen therapy response. ( 19966015 )
2010
18
AND-34/BCAR3 differs from other NSP homologs in induction of anti-estrogen resistance, cyclin D1 promoter activation and altered breast cancer cell morphology. ( 17427198 )
2007
19
AND-34 activates phosphatidylinositol 3-kinase and induces anti-estrogen resistance in a SH2 and GDP exchange factor-like domain-dependent manner. ( 15671247 )
2005
20
Creation of estrogen resistance in vivo by transgenic overexpression of the heterogeneous nuclear ribonucleoprotein-related estrogen response element binding protein. ( 15976060 )
2005
21
[Estrogen resistance and aromatase deficiency in humans]. ( 12462077 )
2002
22
BCAR1, a human homologue of the adapter protein p130Cas, induces anti-estrogen resistance in breast cancer cells. ( 10639512 )
2000
23
Aromatase deficiency and estrogen resistance: from molecular genetics to clinic. ( 11305285 )
2000
24
Reversal of estrogen-resistance in murine mammary adenocarcinomas. ( 10424399 )
1999
25
Identification of a novel breast-cancer-anti-estrogen-resistance (BCAR2) locus by cell-fusion-mediated gene transfer in human breast-cancer cells. ( 9259413 )
1997
26
Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. ( 8090165 )
1994
27
R-verapamil decreases anti-estrogen resistance in a breast cancer model. ( 1676580 )
1991

Variations for Estrogen Resistance

UniProtKB/Swiss-Prot genetic disease variations for Estrogen Resistance:

76
# Symbol AA change Variation ID SNP ID
1 ESR1 p.Gln375His VAR_070072 rs397509428
2 ESR1 p.Arg394His VAR_078516 rs113169205

ClinVar genetic disease variations for Estrogen Resistance:

6 (show all 26)
# Gene Variation Type Significance SNP ID Assembly Location
1 ESR1 NM_001122742.1(ESR1): c.469C> T (p.Arg157Ter) single nucleotide variant Pathogenic rs104893956 GRCh37 Chromosome 6, 152163748: 152163748
2 ESR1 NM_001122742.1(ESR1): c.469C> T (p.Arg157Ter) single nucleotide variant Pathogenic rs104893956 GRCh38 Chromosome 6, 151842613: 151842613
3 ESR1 NM_001122742.1(ESR1): c.1091T> A (p.Val364Glu) single nucleotide variant Uncertain significance rs121913044 GRCh37 Chromosome 6, 152265638: 152265638
4 ESR1 NM_001122742.1(ESR1): c.1091T> A (p.Val364Glu) single nucleotide variant Uncertain significance rs121913044 GRCh38 Chromosome 6, 151944503: 151944503
5 ESR1 NM_000125.3(ESR1): c.1125G> T (p.Gln375His) single nucleotide variant Pathogenic rs397509428 GRCh37 Chromosome 6, 152332819: 152332819
6 ESR1 NM_000125.3(ESR1): c.1125G> T (p.Gln375His) single nucleotide variant Pathogenic rs397509428 GRCh38 Chromosome 6, 152011684: 152011684
7 CCDC170; ESR1 NM_025059.3(CCDC170): c.1710+1144T> G single nucleotide variant Uncertain significance rs12662670 GRCh37 Chromosome 6, 151918856: 151918856
8 CCDC170; ESR1 NM_025059.3(CCDC170): c.1710+1144T> G single nucleotide variant Uncertain significance rs12662670 GRCh38 Chromosome 6, 151597721: 151597721
9 CCDC170 NM_025059.3(CCDC170): c.1810G> A (p.Val604Ile) single nucleotide variant Likely pathogenic rs6929137 GRCh37 Chromosome 6, 151936677: 151936677
10 CCDC170 NM_025059.3(CCDC170): c.1810G> A (p.Val604Ile) single nucleotide variant Likely pathogenic rs6929137 GRCh38 Chromosome 6, 151615542: 151615542
11 CCDC170 NM_025059.3(CCDC170): c.*68A> C single nucleotide variant Uncertain significance rs3734805 GRCh37 Chromosome 6, 151939350: 151939350
12 CCDC170 NM_025059.3(CCDC170): c.*68A> C single nucleotide variant Uncertain significance rs3734805 GRCh38 Chromosome 6, 151618215: 151618215
13 CCDC170 NM_025059.3(CCDC170): c.*978A> G single nucleotide variant Uncertain significance rs9383589 GRCh37 Chromosome 6, 151940260: 151940260
14 CCDC170 NM_025059.3(CCDC170): c.*978A> G single nucleotide variant Uncertain significance rs9383589 GRCh38 Chromosome 6, 151619125: 151619125
15 CCDC170 NC_000006.12: g.151625494T> A single nucleotide variant Uncertain significance rs12665607 GRCh37 Chromosome 6, 151946629: 151946629
16 CCDC170 NC_000006.12: g.151625494T> A single nucleotide variant Uncertain significance rs12665607 GRCh38 Chromosome 6, 151625494: 151625494
17 CCDC170 NC_000006.12: g.151627231G> A single nucleotide variant Likely pathogenic rs2046210 GRCh37 Chromosome 6, 151948366: 151948366
18 CCDC170 NC_000006.12: g.151627231G> A single nucleotide variant Likely pathogenic rs2046210 GRCh38 Chromosome 6, 151627231: 151627231
19 CCDC170 NC_000006.12: g.151630085A> G single nucleotide variant Uncertain significance rs9397435 GRCh37 Chromosome 6, 151951220: 151951220
20 CCDC170 NC_000006.12: g.151630085A> G single nucleotide variant Uncertain significance rs9397435 GRCh38 Chromosome 6, 151630085: 151630085
21 ESR1 NM_000125.3(ESR1): c.1181G> A (p.Arg394His) single nucleotide variant Pathogenic/Likely pathogenic rs1131692059 GRCh37 Chromosome 6, 152332875: 152332875
22 ESR1 NM_000125.3(ESR1): c.1181G> A (p.Arg394His) single nucleotide variant Pathogenic/Likely pathogenic rs1131692059 GRCh38 Chromosome 6, 152011740: 152011740
23 ESR1 NM_000125.3(ESR1): c.*241T> A single nucleotide variant risk factor GRCh37 Chromosome 6, 152420342: 152420342
24 ESR1 NM_000125.3(ESR1): c.*241T> A single nucleotide variant risk factor GRCh38 Chromosome 6, 152099207: 152099207
25 TMEM59 NM_001305049.1(TMEM59): c.*23G> A single nucleotide variant risk factor GRCh37 Chromosome 1, 54497800: 54497800
26 TMEM59 NM_001305049.1(TMEM59): c.*23G> A single nucleotide variant risk factor GRCh38 Chromosome 1, 54032127: 54032127

Expression for Estrogen Resistance

Search GEO for disease gene expression data for Estrogen Resistance.

Pathways for Estrogen Resistance

Pathways related to Estrogen Resistance according to KEGG:

38
# Name Kegg Source Accession
1 Endocrine resistance hsa01522
2 Prolactin signaling pathway hsa04917
3 Estrogen signaling pathway hsa04915

Pathways related to Estrogen Resistance according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.13 BCAR1 BCAR3
2 10.04 BCAR1 ESR1

GO Terms for Estrogen Resistance

Sources for Estrogen Resistance

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
Content
Loading form....